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Genetically elevated fetuin-A levels, fasting glucose levels, and risk of type 2 diabetes: the cardiovascular health study.
Tuesday,2013-08-13 17:40 America/Los_Angeles — eenright
| Title | Genetically elevated fetuin-A levels, fasting glucose levels, and risk of type 2 diabetes: the cardiovascular health study. |
| Publication Type | Journal Article |
| Year of Publication | 2013 |
| Authors | Jensen, MK, Bartz, TM, Djoussé, L, Kizer, JR, Zieman, SJ, Rimm, EB, Siscovick, DS, Psaty, BM, Ix, JH, Mukamal, KJ |
| Journal | Diabetes Care |
| Volume | 36 |
| Issue | 10 |
| Pagination | 3121-7 |
| Date Published | 2013 Oct |
| ISSN | 1935-5548 |
| Keywords | alpha-2-HS-Glycoprotein, Blood Glucose, Diabetes Mellitus, Type 2, Fasting, Female, Genotype, Humans, Male, Polymorphism, Single Nucleotide |
| Abstract | <p><b>OBJECTIVE: </b>Fetuin-A levels are associated with higher risk of type 2 diabetes, but it is unknown if the association is causal. We investigated common (>5%) genetic variants in the fetuin-A gene (AHSG) fetuin-A levels, fasting glucose, and risk of type 2 diabetes.</p><p><b>RESEARCH DESIGN AND METHODS: </b>Genetic variation, fetuin-A levels, and fasting glucose were assessed in 2,893 Caucasian and 542 African American community-living individuals 65 years of age or older in 1992-1993.</p><p><b>RESULTS: </b>Common AHSG variants (rs4917 and rs2248690) were strongly associated with fetuin-A concentrations (P<0.0001). In analyses of 259 incident cases of type 2 diabetes, the single nucleotide polymorphisms (SNPs) were not associated with diabetes risk during follow-up and similar null associations were observed when 579 prevalent cases were included. As expected, higher fetuin-A levels were associated with higher fasting glucose concentrations (1.9 mg/dL [95% CI, 1.2-2.7] higher per SD in Caucasians), but Mendelian randomization analyses using both SNPs as unbiased proxies for measured fetuin-A did not support an association between genetically predicted fetuin-A levels and fasting glucose (-0.3 mg/dL [95% CI, -1.9 to 1.3] lower per SD in Caucasians). The difference between the associations of fasting glucose with actual and genetically predicted fetuin-A level was statistically significant (P=0.001). Results among the smaller sample of African Americans trended in similar directions but were statistically insignificant.</p><p><b>CONCLUSIONS: </b>Common variants in the AHSG gene are strongly associated with plasma fetuin-A concentrations, but not with risk of type 2 diabetes or glucose concentrations, raising the possibility that the association between fetuin-A and type 2 diabetes may not be causal.</p> |
| DOI | 10.2337/dc12-2323 |
| Alternate Journal | Diabetes Care |
| PubMed ID | 23801724 |
| PubMed Central ID | PMC3781539 |
| Grant List | N01HC55222 / HC / NHLBI NIH HHS / United States N01HC85080 / HC / NHLBI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States HHSN268200800007C / HL / NHLBI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States R01 HL094555 / HL / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States N01HC85081 / HC / NHLBI NIH HHS / United States N01HC85079 / HC / NHLBI NIH HHS / United States HHSN268201200036C / HL / NHLBI NIH HHS / United States N01HC85086 / HC / NHLBI NIH HHS / United States N01HC65226 / HL / NHLBI NIH HHS / United States R01 HL080295 / HL / NHLBI NIH HHS / United States N01HC85082 / HC / NHLBI NIH HHS / United States HHSN268200800007C / / PHS HHS / United States N01HC85082 / HL / NHLBI NIH HHS / United States N01HC85083 / HL / NHLBI NIH HHS / United States HHSN268201200036C / / PHS HHS / United States HL080295 / HL / NHLBI NIH HHS / United States N01HC85083 / HC / NHLBI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States N01HC85080 / HL / NHLBI NIH HHS / United States AG023629 / AG / NIA NIH HHS / United States R56 AG023629 / AG / NIA NIH HHS / United States N01HC65226 / HC / NHLBI NIH HHS / United States N01HC85081 / HL / NHLBI NIH HHS / United States |